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Journal articles
The human immune response to Dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity.
Martina Beltramello
1
Katherine L. Williams
2
Cameron P. Simmons
3
Annalisa Macagno
1
Luca Simonelli
1
Nguyen Than Ha Quyen
3
Soila Sukupolvi-Petty
4
Erika Navarro-Sanchez
5
Paul R. Young
6
Aravinda M. de Silva
7
Félix A. Rey
5
Luca Varani
Stephen S Whitehead
8
Michael S. Diamond
4
Eva Harris
2
Antonio Lanzavecchia
1, *
Federica Sallusto
1, *
*
Corresponding author
Martina Beltramello 1
Author
Katherine L. Williams 2
Author
Cameron P. Simmons 3
Author
Annalisa Macagno 1
Author
Luca Simonelli 1
Author
Nguyen Than Ha Quyen 3
Author
Soila Sukupolvi-Petty 4
Author
Erika Navarro-Sanchez 5
Author
Stephen S Whitehead 8
Author
Michael S. Diamond 4
Author
Eva Harris 2
Author
Antonio Lanzavecchia 1
Correspondent author
Federica Sallusto 1
Correspondent author
1
Institute for Research in Biomedicine (Bellinzona 6500 - Switzerland)
2
Division of Infectious Diseases [Berkeley] (Berkeley, CA 94720-7354 - United States)
- School of Public Health [Berkeley] (Berkeley CA - United States)
- University of California [Berkeley] (Berkeley, CA - United States)
- University of California (United States)
- University of California [Berkeley] (Berkeley, CA - United States)
3
OUCRU - Oxford University Clinical Research Unit [Ho Chi Minh City] (190 Ben Ham Tu, District 5, Ho Chi Minh City - Vietnam)
4
Departments of Medicine, Molecular Microbiology, Pathology & Immunology (St. Louis, MO 63110 - United States)
5
Virologie Structurale (25-28 rue du Docteur Roux, F-75724 Paris cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- CNRS - Centre National de la Recherche Scientifique : URA3015 (France)
6
Centre for Infectious Disease Research (School of Chemistry and Molecular Biosciences, Brisbane, Queensland 4072 - Australia)
- University of Queensland [Brisbane] (Brisbane, St Lucia, QLD 4072 - Australia)
7
Department of Microbiology and Immunology (Chapel Hill, NC 27599 - United States)
- UNC - University of North Carolina [Chapel Hill] (250 East Franklin Street, Chapel Hill, NC, - United States)
- UNC - University of North Carolina System (United States)
8
Laboratory of Infectious Diseases (National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-8133 - United States)
- National Institute of Health (France)
Abstract : Antibodies protect against homologous Dengue virus (DENV) infection but can precipitate severe dengue by promoting heterotypic virus entry via Fcγ receptors (FcγR). We immortalized memory B cells from individuals after primary or secondary infection and analyzed anti-DENV monoclonal antibodies (mAbs) thus generated. MAbs to envelope (E) protein domain III (DIII) were either serotype specific or cross-reactive and potently neutralized DENV infection. DI/DII- or viral membrane protein prM-reactive mAbs neutralized poorly and showed broad cross-reactivity with the four DENV serotypes. All mAbs enhanced infection at subneutralizing concentrations. Three mAbs targeting distinct epitopes on the four DENV serotypes and engineered to prevent FcγR binding did not enhance infection and neutralized DENV in vitro and in vivo as postexposure therapy in a mouse model of lethal DENV infection. Our findings reveal an unexpected degree of cross-reactivity in human antibodies against DENV and illustrate the potential for an antibody-based therapy to control severe dengue.
Document type :
Journal articles
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00530282
Contributor : Mireille Gau Connect in order to contact the contributor
Submitted on : Thursday, October 28, 2010 - 11:42:45 AM
Last modification on : Tuesday, October 19, 2021 - 10:25:45 PM
Contributor : Mireille Gau Connect in order to contact the contributor
Submitted on : Thursday, October 28, 2010 - 11:42:45 AM
Last modification on : Tuesday, October 19, 2021 - 10:25:45 PM
Identifiers
- HAL Id : pasteur-00530282, version 1
- DOI : 10.1016/j.chom.2010.08.007
- PUBMED : 20833378
Citation
Martina Beltramello, Katherine L. Williams, Cameron P. Simmons, Annalisa Macagno, Luca Simonelli, et al.. The human immune response to Dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity.. Cell Host and Microbe, Elsevier, 2010, 8 (3), pp.271-83. ⟨10.1016/j.chom.2010.08.007⟩. ⟨pasteur-00530282⟩
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